AIM: To study the sensitivity of gastric smooth muscle to C-type natriuretic peptide (CNP) in streptozotocin (STZ)-induced diabetic rats. METHODS: The spontaneous contraction of a gastric smooth muscle strip was recor...AIM: To study the sensitivity of gastric smooth muscle to C-type natriuretic peptide (CNP) in streptozotocin (STZ)-induced diabetic rats. METHODS: The spontaneous contraction of a gastric smooth muscle strip was recorded by using physiological methods in rats. The expressions of CNP and natriuretic peptide receptor-B (NPR-B) in gastric tissue were examined by using immunohistochemistry techniques in the diabetic rat. RESULTS: At 4 wk after injection of STZ and vehicle, the frequency of spontaneous contraction of gastric smooth muscle was significantly reduced in diabetic rats, and the frequency was decreased from 3.10 ± 0.14 cycle/min in controls to 2.23 ± 0.13 cycle/min (n = 8, P < 0.01). However, the amplitude of spontaneous contraction was not significant different from the normal rat. CNP significantly inhibited spontaneous contraction of gastric smooth muscle in normal and diabetic rats, but the inhibitory effect was significantly potentiated in the diabetic rats. The amplitudes of spontaneous contraction were suppressed by 75.15% ± 0.71% and 58.92% ± 1.32% while the frequencies were decreased by 53.33% ± 2.03% and 26.95% ± 2.82% in diabetic and normal rats, respectively (n = 8, P < 0.01). The expression of CNP in gastric tissue was not changed in diabetic rats, however the expression of NPR-B was significantly increased in diabetic rats, and the staining indexes of NPR-B were 30.67 ± 1.59 and 17.63 ± 1.49 in diabetic and normal rat, respectively (n = 8, P < 0.01).CONCLUSION: The results suggest that CNP induced an inhibitory effect on spontaneous contraction of gastric smooth muscle, potentiated in diabetic rat via up-regulation of the natriuretic peptides-NPR-B-particulate guanylyl cyclase-cyclic GMP signal pathway.展开更多
AIM: To investigate the effect and the possible mechanism of ginsenoside Rb1 on small intestinal smooth muscle motility in mice. METHODS: Intestinal smooth muscle strips were isolated from male ICR mice (5 wk old), an...AIM: To investigate the effect and the possible mechanism of ginsenoside Rb1 on small intestinal smooth muscle motility in mice. METHODS: Intestinal smooth muscle strips were isolated from male ICR mice (5 wk old), and the effect of ginsenoside Rb1 on spontaneous contraction was recorded with an electrophysiolograph. The effect of ginsenoside Rb1 on ion channel currents, including the voltage-gated K + channel current (IK V ), calcium-activated potassium channel currents (IK Ca ), spontaneous transient outward currents and ATP-sensitive potassium channel current (IK ATP ), was recorded on freshly isolated single cells using the whole-cell patch clamp technique. RESULTS: Ginsenoside Rb1 dose-dependently inhibited the spontaneous contraction of intestinal smooth muscle by 21.15% ± 3.31%, 42.03% ± 8.23% and 67.23% ± 5.63% at concentrations of 25 μmol/L, 50 μmol/L and 100 μmol/L, respectively (n=5,P<0.05). The inhibitory effect of ginsenoside Rb1 on spontaneous contraction was significantly but incompletely blocked by 10 mmol/L tetraethylammonium or 0.5 mmol/L 4-aminopyridine, respectively (n=5, P<0.05). However, the inhibitory effect of ginsenoside Rb1 on spontaneous contraction was not affected by 10 μmol/L glibenclamide or 0.4 μmol/L tetrodotoxin. At the cell level, ginsenoside Rb1 increased outward potassium currents, and IK V was enhanced from 1137.71 ± 171.62 pA to 1449.73 ± 162.39 pA by 50 μmol/L Rb1 at +60 mV (n=6, P<0.05). Ginsenoside Rb1 increased IK Ca and enhanced the amplitudes of spontaneous transient outward currents from 582.77 ± 179.09 mV to 788.12 ± 278.34 mV (n=5, P<0.05). However, ginsenoside Rb1 (50 μmol/L) had no significant effect on IK ATP (n=3, P<0.05). CONCLUSION: These results suggest that ginsenoside Rb1 has an inhibitory effect on the spontaneous contraction of mouse intestinal smooth muscle mediated by the activation of IK V and IK Ca , but the K ATP channel was not involved in this effect.展开更多
AIM: To investigate the effect of gingerol on colonic motility and the action of L-type calcium channel currents in this process.METHODS: The distal colon was cut along the mesenteric border and cleaned with Ca^(2+)-f...AIM: To investigate the effect of gingerol on colonic motility and the action of L-type calcium channel currents in this process.METHODS: The distal colon was cut along the mesenteric border and cleaned with Ca^(2+)-free physiological saline solution. Muscle strips were removed and placed in Ca^(2+)-free physiological saline solution, which was oxygenated continuously. Longitudinal smooth muscle samples were prepared by cutting along the muscle strips and were then placed in a chamber. Mechanical contractile activities of isolated colonic segments in rats were recorded by a 4-channel physiograph. Colon smooth muscle cells were dissociated by enzymatic digestion. L-type calcium currents were recorded using the conventional whole-cell patch-clamp technique.RESULTS: Gingerol inhibited the spontaneous contraction of colonic longitudinal smooth muscle in a dose-dependent manner with inhibition percentages of 13.3% ± 4.1%, 43.4% ± 3.9%, 78.2% ± 3.6% and 80.5% ± 4.5% at 25 μmol/L, 50 μmol/L, 75 μmol/L and 100 μmol/L, respectively(P < 0.01). Nifedipine, an L-type calcium channel blocker, diminished the inhibition of colonic motility by gingerol. Gingerol inhibited L-type calcium channel currents in colonic longitudinal myocytes of rats. At a 75 μmol/L concentration of gingerol, the percentage of gingerolinduced inhibition was diminished by nifedipine from 77.1% ± 4.2% to 42.6% ± 3.6%(P < 0.01). Gingerol suppressed IBa in a dose-dependent manner, and the inhibition rates were 22.7% ± 2.38%, 35.77% ± 3.14%, 49.78% ± 3.48% and 53.78% ± 4.16% of control at 0 m V, respectively, at concentrations of 25 μmol/L, 50 μmol/L, 75 μmol/L and 100 μmol/L(P < 0.01). The steady-state activation curve was shifted to the right by treatment with gingerol. The value of half activation was-14.23 ± 1.12 m V in the control group and-10.56 ± 1.04 m V in the 75 μmol/L group(P < 0.05) with slope factors, Ks, of 7.16 ± 0.84 and 7.02 ± 0.93(P < 0.05) in the control and 75 μmol/L groups, respectively. However, the steady-stat展开更多
The spontaneous oscillatory contraction（SPOC） of myofibrils is the essential property inherent to the contractile system of muscle. Muscle contraction results from cyclic interactions between actin filament and myos...The spontaneous oscillatory contraction（SPOC） of myofibrils is the essential property inherent to the contractile system of muscle. Muscle contraction results from cyclic interactions between actin filament and myosin II which is a dimeric motor protein with two heads. Taking the two heads of myosin II as an indivisible element and considering the effects of cooperative behavior between the two heads on rate constants in the mechanochemical cycle, the present work proposes the tenstate mechanochemical cycle model for myosin II dimer. The simulations of this model show that the proportion of myosin II in different states periodically changes with time, which results in the sustained oscillations of contractive tension, and serves as the primary factor for SPOC. The good fit of this model to experimental results suggests that the cooperative interaction between the two heads of myosin II dimer may be one of the underlying mechanisms for muscle contraction.展开更多
基金Supported by The National Natural Science Foundation of China, No. 30760068
文摘AIM: To study the sensitivity of gastric smooth muscle to C-type natriuretic peptide (CNP) in streptozotocin (STZ)-induced diabetic rats. METHODS: The spontaneous contraction of a gastric smooth muscle strip was recorded by using physiological methods in rats. The expressions of CNP and natriuretic peptide receptor-B (NPR-B) in gastric tissue were examined by using immunohistochemistry techniques in the diabetic rat. RESULTS: At 4 wk after injection of STZ and vehicle, the frequency of spontaneous contraction of gastric smooth muscle was significantly reduced in diabetic rats, and the frequency was decreased from 3.10 ± 0.14 cycle/min in controls to 2.23 ± 0.13 cycle/min (n = 8, P < 0.01). However, the amplitude of spontaneous contraction was not significant different from the normal rat. CNP significantly inhibited spontaneous contraction of gastric smooth muscle in normal and diabetic rats, but the inhibitory effect was significantly potentiated in the diabetic rats. The amplitudes of spontaneous contraction were suppressed by 75.15% ± 0.71% and 58.92% ± 1.32% while the frequencies were decreased by 53.33% ± 2.03% and 26.95% ± 2.82% in diabetic and normal rats, respectively (n = 8, P < 0.01). The expression of CNP in gastric tissue was not changed in diabetic rats, however the expression of NPR-B was significantly increased in diabetic rats, and the staining indexes of NPR-B were 30.67 ± 1.59 and 17.63 ± 1.49 in diabetic and normal rat, respectively (n = 8, P < 0.01).CONCLUSION: The results suggest that CNP induced an inhibitory effect on spontaneous contraction of gastric smooth muscle, potentiated in diabetic rat via up-regulation of the natriuretic peptides-NPR-B-particulate guanylyl cyclase-cyclic GMP signal pathway.
基金Supported by The National Natural Science Foundation of China, No. 30873328The State Administration of Traditional Chinese Medicine of the People’s Republic of China, No. 06-075930
文摘AIM: To investigate the effect and the possible mechanism of ginsenoside Rb1 on small intestinal smooth muscle motility in mice. METHODS: Intestinal smooth muscle strips were isolated from male ICR mice (5 wk old), and the effect of ginsenoside Rb1 on spontaneous contraction was recorded with an electrophysiolograph. The effect of ginsenoside Rb1 on ion channel currents, including the voltage-gated K + channel current (IK V ), calcium-activated potassium channel currents (IK Ca ), spontaneous transient outward currents and ATP-sensitive potassium channel current (IK ATP ), was recorded on freshly isolated single cells using the whole-cell patch clamp technique. RESULTS: Ginsenoside Rb1 dose-dependently inhibited the spontaneous contraction of intestinal smooth muscle by 21.15% ± 3.31%, 42.03% ± 8.23% and 67.23% ± 5.63% at concentrations of 25 μmol/L, 50 μmol/L and 100 μmol/L, respectively (n=5,P<0.05). The inhibitory effect of ginsenoside Rb1 on spontaneous contraction was significantly but incompletely blocked by 10 mmol/L tetraethylammonium or 0.5 mmol/L 4-aminopyridine, respectively (n=5, P<0.05). However, the inhibitory effect of ginsenoside Rb1 on spontaneous contraction was not affected by 10 μmol/L glibenclamide or 0.4 μmol/L tetrodotoxin. At the cell level, ginsenoside Rb1 increased outward potassium currents, and IK V was enhanced from 1137.71 ± 171.62 pA to 1449.73 ± 162.39 pA by 50 μmol/L Rb1 at +60 mV (n=6, P<0.05). Ginsenoside Rb1 increased IK Ca and enhanced the amplitudes of spontaneous transient outward currents from 582.77 ± 179.09 mV to 788.12 ± 278.34 mV (n=5, P<0.05). However, ginsenoside Rb1 (50 μmol/L) had no significant effect on IK ATP (n=3, P<0.05). CONCLUSION: These results suggest that ginsenoside Rb1 has an inhibitory effect on the spontaneous contraction of mouse intestinal smooth muscle mediated by the activation of IK V and IK Ca , but the K ATP channel was not involved in this effect.
基金Supported by National Basic Research Program of China(973 Program)No.2013CB531703+3 种基金National Natural Science Foundation of ChinaNo.81273919Natural Science Foundation of Liaoning ProvinceNo.2012225020 and No.2013023002
文摘AIM: To investigate the effect of gingerol on colonic motility and the action of L-type calcium channel currents in this process.METHODS: The distal colon was cut along the mesenteric border and cleaned with Ca^(2+)-free physiological saline solution. Muscle strips were removed and placed in Ca^(2+)-free physiological saline solution, which was oxygenated continuously. Longitudinal smooth muscle samples were prepared by cutting along the muscle strips and were then placed in a chamber. Mechanical contractile activities of isolated colonic segments in rats were recorded by a 4-channel physiograph. Colon smooth muscle cells were dissociated by enzymatic digestion. L-type calcium currents were recorded using the conventional whole-cell patch-clamp technique.RESULTS: Gingerol inhibited the spontaneous contraction of colonic longitudinal smooth muscle in a dose-dependent manner with inhibition percentages of 13.3% ± 4.1%, 43.4% ± 3.9%, 78.2% ± 3.6% and 80.5% ± 4.5% at 25 μmol/L, 50 μmol/L, 75 μmol/L and 100 μmol/L, respectively(P < 0.01). Nifedipine, an L-type calcium channel blocker, diminished the inhibition of colonic motility by gingerol. Gingerol inhibited L-type calcium channel currents in colonic longitudinal myocytes of rats. At a 75 μmol/L concentration of gingerol, the percentage of gingerolinduced inhibition was diminished by nifedipine from 77.1% ± 4.2% to 42.6% ± 3.6%(P < 0.01). Gingerol suppressed IBa in a dose-dependent manner, and the inhibition rates were 22.7% ± 2.38%, 35.77% ± 3.14%, 49.78% ± 3.48% and 53.78% ± 4.16% of control at 0 m V, respectively, at concentrations of 25 μmol/L, 50 μmol/L, 75 μmol/L and 100 μmol/L(P < 0.01). The steady-state activation curve was shifted to the right by treatment with gingerol. The value of half activation was-14.23 ± 1.12 m V in the control group and-10.56 ± 1.04 m V in the 75 μmol/L group(P < 0.05) with slope factors, Ks, of 7.16 ± 0.84 and 7.02 ± 0.93(P < 0.05) in the control and 75 μmol/L groups, respectively. However, the steady-stat
基金Project supported by Research Program of Science and Technology at Universities of Inner Mongolia Autonomous Region,China(Grant Nos.NJZY16493and NJZC17458)
文摘The spontaneous oscillatory contraction（SPOC） of myofibrils is the essential property inherent to the contractile system of muscle. Muscle contraction results from cyclic interactions between actin filament and myosin II which is a dimeric motor protein with two heads. Taking the two heads of myosin II as an indivisible element and considering the effects of cooperative behavior between the two heads on rate constants in the mechanochemical cycle, the present work proposes the tenstate mechanochemical cycle model for myosin II dimer. The simulations of this model show that the proportion of myosin II in different states periodically changes with time, which results in the sustained oscillations of contractive tension, and serves as the primary factor for SPOC. The good fit of this model to experimental results suggests that the cooperative interaction between the two heads of myosin II dimer may be one of the underlying mechanisms for muscle contraction.
